A group of investigators at the Wadsworth Center are requesting funds to purchase a JEOL JEM-1400 transmission electron microscope (TEM). The major users of this instrument include five NIH-funded laboratories with extensive track records in, and whose specific aims require analyses by electron microscopy using multiple conventional thin-section and cryo approaches. Until the end of 2008, two microscopes at Wadsworth were available for these projects. One of these, a 24-year-old Philips EM420, has reached the end of its service life, and was decommissioned at the end of 2008. The other TEM, a 14- year-old Zeiss 910 that, despite being covered by a comprehensive service plan, has become so unreliable that its downtime (66% in 2008) represents a significant barrier to research progress. Moreover, the Zeiss 910 cannot be used for the cryo work formerly performed on the EM420. The JEOL JEM-1400 is an ideal replacement for the Zeiss 910, because it will readily accommodate both conventional and cryo modes of operation. This instrument is vital as it accepts a specimen holder that can load up to five grids at one time. For the three major users that perform extensive serial-section analyses, this feature represents a significant functional improvement. A cost-effective 2k x 2k digital camera is also included, particularly for the tomographic and single-particle cryo-EM projects. This instrument will be integrated into a long- standing EM Core, with local administrative and oversight committees to ensure appropriate use and maintenance. The Wadsworth Center is strongly committed to the addition of the JEM-1400. As evidence of support, the Center will provide a State-funded, experienced, Research Scientist to oversee the instrument's operation, assume costs associated with the annual service contract, and provide additional funds to purchase the cryo stage, controller, and dry pumping station equipment that are required for three of the five major users. In addition, and as time permits, this instrument will be made available to other funded investigators with assistance from a dedicated EM Core, thus enhancing the Wadsworth Center's long-standing use of electron microscopy as a research tool.